Cb4(+)CD25(+)regulatory T cells (Treg) contributes in homeostasis of the immune system by controlling an immune response. Recent accumulated findings suggest naturally occurring CD4(+)CD25(+)regulatory T cells which develop at least in the thymus via autoreactivity positive selection consists of an distinct T cell subset. As it is known that transcription factors contribute in the determination of cell lineage and transduction of the transcription factors induces cell differentiation. In order to find Treg-specific transcription factors, we generated Treg-specific expression cDNA library by subtraction. Among the library, we found two factors ; the one is (189), and the other is FOXP3. Foxp3 is demonstrated to play a pivotal role in Treg development. Therefore, we subsequently extended our research to screen FOXP3-assocaited molecules. By two yeast hybrid, we found SOCS3 is associated with FOXP3. The association involves SH2 region of SOCS3 and 81-210 amino acids region of FOXP3. Furthermore, We found that FOXP3 is associated the endogenous SOCS3 in FOXP3-transfected Treg cell clone. Considering the role of SOCS3 in the signal transduction, it is of interest to imagine that SOCS3 contribute in the immune regulation via Treg development.